What question did this study set out to answer?

To explore the interactions between the immune system and microbiota in ileal tissues of Crohn’s disease patients.

January 23, 2026

P0015The Dynamics of the Immune-Microbiota Axis in Ileal Tissue Layers of Patients with Crohn’s Disease

Key Points

To explore the interactions between the immune system and microbiota in ileal tissues of Crohn’s disease patients.
Enrolled 28 patients with Crohn’s disease, collecting damaged and non-damaged mucosal tissues and blood samples.
Assessed bacterial composition via 16S rRNA gene amplicon sequencing.
Evaluated systemic microRNA levels using quantitative real-time PCR amplification.
Analyzed free fatty acids through gas chromatography-mass spectrometry.
Performed a comprehensive cytokine profile analysis in select patients using multiplex assays.
Healthy ileal mucosa had a richer microbiota compared to inflamed tissue.
Pathological conditions showed higher levels of Tenericutes and specific genera such as Mesoplasma and Mycoplasma.
Significant differences in bacteria between relapse and initial surgery patients regarding specific families and genera.
Downregulation of circulating microRNAs (miR-155 and miR-223) and certain fatty acids noted in relapse cases.
Distinct profiles of several cytokines and inflammatory markers found between Crohn's and healthy tissues, and among patient groups.

Abstract

Abstract Background The pathogenesis of Crohn’s Disease (CD) remains unclear. However, disruption in the mucosal immune system’s interaction with the gut microbiota is suspected to be a key factor in tissue injury. The study aims to characterize the ileal microbiota and the immune response (both locally and systemically) by comparing diseased and healthy tissue, specifically differentiating between patients undergoing first-time surgery and those experiencing relapse. Methods We enrolled 28 CD patients and collected damaged and non-damaged mucosa tissues and blood samples. Bacterial composition was assessed through amplicon sequencing of the 16S rRNA gene. In addition, we evaluated the systemic microRNA (miRNA) using quantitative real-time PCR amplification and free fatty acids (FFAs) using gas chromatography-mass spectroscopy.Finally, in a restricted number of patients, a comprehensive analysis of an ileal mucosa, submucosa and serosa broad-spectrum cytokine panel was performed by multiplex approach. Results The mucosal adherent microbiota was enriched in healthy compared to inflamed mucosa. In contrast, the phylum Tenericutes, the family Ruminococcaceae, and the genera Mesoplasma and Mycoplasma were significantly enriched in the pathological setting. Significant microbiota differences were observed between the relapse and first surgery patients regarding the families Bacillaceae 2 and Brucellaceae and the genera Escherichia/Shigella, Finegoldia, Antrobacter, Gemmatimonas, Moraxella, Anoxibacillus, and Proteus. We observed a significant downregulation of circulating miR-155 and miR-223, as well as 2-methyl butyric, isobutyric, and hexanoic (caproic) acids in recurrence compared to the first surgery patients. At local level, we observed a distinct profile of IL1-α, IL-1β, IL-4, IL-8, ICAM-1, E-Selectin, P-Selectin, IP-10, IL 6 and IL 18 across the CD vs healthy ileal layers; and a different distribution of IFN- γ, P-Selectin, IL-27 and IL-21 in first surgery vs relapse patients. Conclusion We found distinct differences in ileal microbiota composition when comparing CD and healthy tissues, along with variations in systemic microbial-associated inflammatory factors between first-time surgery and surgical relapse. Our data suggest that specific microbiota patterns associated with otherwise healthy ileal tissue may play a role in triggering CD recurrence. These findings offer new insights into the gut microbiota-immunity axis in CD relapse, which could pave the way for novel diagnostics and therapeutics focused not just on reducing inflammation, but also on actively maintaining a state of eubiosis (microbial balance) in healthy intestinal tissue. Conflict of interest: Prof. Amedei, Amedeo: No conflict of interest Giudici, Francesco: No conflict of interest Nannini, Giulia: I I have no conflict of interest Baldi, Simone: No conflict of interest Niccolai, Elena: No conflict of interest Bartalucci, Gianluca: No conflict of interest Ramazzotti, Matteo: No conflict of interest

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